The effect of recombinant erythropoietin on long-term outcome after moderate-to-severe traumatic brain injury
Authors: Markus B. Skrifvars, Nora Luethi, Michael Bailey, Craig French, Alistair Nichol, Tony Trapani, Colin McArthur, Yaseen M. Arabi, Stepani Bendel, David J. Cooper, Rinaldo Bellomo, Colin McArthur Lynette Newby, Frank Van Haren, Shakira Spiller, Mary Nourse, Josie Russell Brown, Seton Henderson, Jan Mehrtens, David Silverman, Robyn Hutchinson, Brent Richards, Mandy Tallott, Jonathan Field, Markus Skrifvars, Heikki Vartiala, Marianne Eliasson, Mika Koivikko, Peter Harrigan, Miranda Hardie, Adam Tolfree, Yaseen Arabi, Samir Haddad, Marwan Al Kishi, Ahmad Deeb, Shmeylan Al Harbi, Lolowa Al-Swaidan, Turki Al Moammar, Juliet Lingling, Shella Caliwag, Hanie Richi, Asma Al Jandan, Stepani Bendel, Sari Rahikainen, Victor Tam, Jacqui Robinson, Victor Tam, Sharon Micallef, Louise Cole, Leonie Weisbrodt, Rebecca Gresham, Maria Nikas, Anne Richie, Richard Strickland, Justine Rivett, Sonya Kloeden, Stephanie O’Connor, David Cooper, Richard McAllister, Deborah Barge, Jeffrey Presneill, Simon Finfer, Elizabeth Yarad, Simon Bird, Anne O’Connor, Naomi Hammond, Frances Bass, Melanie Boardman, Sharon Waterson, David Gattas, Heidi Buhr, Priya Nair, Claire Reynolds, Robyn Tantau, David James Cooper, Jasmin Board, Shirley Vallance, Phoebe McCracken, Meredith Young, Geoffrey Gordon, Stephen Reeves, Sonja Brennan, Paul Young, Anna Hunt, Nina Beehre, Hannah Smellie, Vineet Nayyar, Christina Whitehead, Jing Kong, George Bonovas, Christina Whitehead, Jing Kong, George Bonovas
Journal: Intensive Care Medicine (2023)

Recombinant erythropoietin (EPO) administered for traumatic brain injury (TBI) may increase short-term survival, but the long-term effect is unknown. We conducted a pre-planned long-term follow-up of patients in the multicentre erythropoietin in TBI trial (2010–2015). We invited survivors to follow-up and evaluated survival and functional outcome with the Glasgow Outcome Scale-Extended (GOSE) (categories 5–8 = good outcome), and secondly, with good outcome determined relative to baseline function (sliding scale). We used survival analysis to assess time to death and absolute risk differences (ARD) to assess favorable outcomes. We categorized TBI severity with the International Mission for Prognosis and Analysis of Clinical Trials in TBI model. Heterogeneity of treatment effects were assessed with interaction p-values based on the following a priori defined subgroups, the severity of TBI, and the presence of an intracranial mass lesion and multi-trauma in addition to TBI. Of 603 patients in the original trial, 487 patients had survival data; 356 were included in the follow-up at a median of 6 years from injury. There was no difference between treatment groups for patient survival [EPO vs placebo hazard ratio (HR) (95% confidence interval (CI) 0.73 (0.47–1.14) p = 0.17]. Good outcome rates were 110/175 (63%) in the EPO group vs 100/181 (55%) in the placebo group (ARD 8%, 95% CI $$-$$ 3 to 18%, p = 0.14). When good outcome was determined relative to baseline risk, the EPO groups had better GOSE (sliding scale ARD 12%, 95% CI 2–22%, p = 0.02). When considering long-term patient survival, there was no evidence for heterogeneity of treatment effect (HTE) according to severity of TBI (p = 0.85), presence of an intracranial mass lesion (p = 0.48), or whether the patient had multi-trauma in addition to TBI (p = 0.08). Similarly, no evidence of treatment heterogeneity was seen for the effect of EPO on functional outcome. EPO neither decreased overall long-term mortality nor improved functional outcome in moderate or severe TBI patients treated in the intensive care unit (ICU). The limited sample size makes it difficult to make final conclusions about the use of EPO in TBI.